1,3-Dibromo-5,5-dimethylhydantoin → 7-Bromo-6-(3-(pyrrolidin-1-yl)propyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine

HRID 1615463Notes

Reaction equation

HRID 1615463 reaction equation
[N:1]1([CH2:6][CH2:7][CH2:8][C:9]2[CH:10]=[C:11]3[N:16]([CH:17]=2)[N:15]=[CH:14][N:13]=[C:12]3[NH2:18])[CH2:5][CH2:4][CH2:3][CH2:2]1.[Br:19]N1C(C)(C)C(=O)N(Br)C1=O>CN(C=O)C>[Br:19][C:17]1[N:16]2[C:11]([C:12]([NH2:18])=[N:13][CH:14]=[N:15]2)=[CH:10][C:9]=1[CH2:8][CH2:7][CH2:6][N:1]1[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

4

Reactant 2

HCID 64791,3-Dibromo-5,5-dimethylhydantoinHCID 666017846-(3-(Pyrrolidin-1-yl)propyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine

Product 1

HCID 666123207-Bromo-6-(3-(pyrrolidin-1-yl)propyl)pyrrolo[2,1-f][1,2,4]triazin-4-amineYield 80.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of the compound (257 mg, 1.05 mmol) prepared in Example 12 in DMF (8 mL) at −78° C. was added 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione (150 mg, 0.52 mmol) portion wise over a period of 5 minutes. The reaction was stirred for 30 minutes and was allowed to warm to room temperature, and stirred overnight. DMF was removed under vacuum, and the crude solid was extracted with DCM/sodium hydroxide (1N) solution. The organic layer was dried, concentrated, and the crude product was purified by prep HPLC. The pure fractions were concentrated, extracted with saturated sodium bicarbonated/DCM, and the organic layer was dried sodium sulfate, filtered and concentrated to obtain the title compound (135 mg) having the following physical data.

Workup

  1. stirringstirred overnight
  2. customDMF was removed under vacuum
  3. extractionthe crude solid was extracted with DCM/sodium hydroxide (1N) solution
  4. customThe organic layer was dried
  5. concentrationconcentrated
  6. customthe crude product was purified by prep HPLC
  7. concentrationThe pure fractions were concentrated
  8. extractionextracted with saturated sodium
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-180010dab0004baab5b882bee28719c4
Source dataset
uspto-grants-2014_07
Patent number
US08765754B2

Reaction notes

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